Smoking Linked to Long-Term Risk of Age-Related Macular Degeneration

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Explain to patients who ask that this study found that age-related macular degeneration, an eye disorder than can lead to blindness and often caused by diabetes, is more common among smokers.

MADISON, Wis., Jan 14 -- Smokers appear to have a 47% increased risk of developing early age-related macular degeneration, and a 43% increased risk in the cumulative 15-year progression of the condition.

The smokers also developed the condition at a younger age than former and never-smokers, Dr. Ronald Klein, M.D., of the University of Wisconsin here, and colleagues in the Beaver Dam Eye Study reported in the January 2008 issue of the Archives of Ophthalmology.

Smoking may contribute to the age-related macular degeneration through immune activation, depression of antioxidant levels, reduction of choroidal blood flow, decrease in luteal pigments in the retina, reduction of drug detoxification by the retinal pigment epithelium, and nicotine potentiation of angiogenic activities, the researchers said.

Following up on observations from shorter observations of the same population-based longitudinal cohort, the investigators studied 4,926 people in Beaver Dam, Wis., who were 43 to 84 years old in 1987 and 1988. At the beginning of the study, 21% of the men and 18% of the women were smokers.

Participants were examined in 1988 to 1990 and were re-examined at five-year intervals for 15 years. Age-related macular degeneration status was determined by grading stereoscopic color fundus photographs.

Controlling for age, sex, and baseline severity of age-related macular degeneration, the researchers found that those who were smokers at baseline, compared with those who never smoked, were at an increased risk of early macular degeneration (odds ratio 1.47, 95% confidence interval 1.08 to 1.99, P=0.01).

The smokers also developed the eye disease at a younger age than former smokers and those who had never smoked, namely 69.2 years for current smokers, 72.3 years for former smokers, and 74.4 years for never-smokers.

Smoking at the study outset was associated with an increased risk of cumulative progression over 15 years of 43% (OR 1.43, 95% CI 1.05 to 1.94, P=0.02), the investigators said. However, there were few associations with outcomes for specific characteristics of smoking, including intensity, pack-years smoked, duration, and age at start and quitting.

The finding that smoking is related to early age-related macular degeneration or progression, the researchers said, is consistent with their earlier 10-year follow-up report and with other studies.

However, as in the earlier study, the researchers could not find an association between smoking and late (severe) macular degeneration.

This may be because most smokers begin quitting by age 65 or older. Also, they suggested that other unmeasured factors, such as inhalation or differences in cigarettes smoked, not measured in this study might, in part, explain these differences.

Finally, they said, it is possible that smoking may not increase the risk of progression of early to late disease in this population.

The researchers noted that smoking status did not appear to affect individuals with exudative disease (63 participants) or geographic atrophy (39), perhaps because of the small number involved. Therefore, the possibility cannot be ruled out, they said.

Exposure to environmental smoke was also not associated with the prevalence, five-year rate, or progression of early macular degeneration in men or women nonsmokers. This may be because of the relatively short five-year follow-up, or perhaps the overall decrease in environmental smoke, they suggested.

Dr. Klein and colleagues emphasized that smoking is one of the few modifiable risk factors associated with the eye disease.

This study was funded by a grant from the National Eye Institute and a grant from the National Institute on Aging and was also supported in part by Research to Prevent Blindness, New York, N.Y.

No financial conflicts were reported.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

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